1. Field of the Invention
The present invention relates to a method for delivering heterologous genes to motor neuron cell bodies using retrograde viral transport. In greater detail, the present invention relates to a method for introducing genes into neurons that innervate muscle tissues by using an adeno-associated virus vector that is capable of retrograde axonal transport. Following introduction, these genes can be expressed in the cell body of the neuron. This method has applications in the treatment of neurodegenerative diseases.
2. Background
A significant number of people worldwide suffer from neurodegenerative diseases. Many of these diseases cause the degeneration of motor neurons, which in turn results in the progressive loss of function of the muscle tissues which are innervated by these motor neurons. A number of neurodegenerative diseases which result in the loss of muscle function are known. Examples of such diseases include muscular dystrophy (MD) and amyotrophic lateral sclerosis (ALS). MD refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. Although the severity of MD varies depending on type, it is often fatal due to respiratory deficit. ALS occurs when specific nerve cells in the brain and spinal cord that control voluntary movement gradually degenerate. The loss of these motor neurons causes the muscles under their control to weaken and waste away, leading to paralysis and eventually death due to paralysis of the muscles involved in respiration. In the United States, ALS affects at least 20,000 individuals.
As more becomes known about the genetic causes of neurodegenerative diseases, the utility of gene therapy as a treatment for such diseases increases. One component of any gene therapy program is delivery of the desired genetic material, such as a replacement gene, to the cells of interest. Neurons present feasible targets for gene delivery, however, given the structure and internal location of most neurons, administration of the gene delivery vector directly to a target neuron is often difficult. For example, intracranial injection must deliver the vector to a specific location without damaging the targeted cells or causing collateral infection of nearby cells. This precision of delivery is difficult to achieve since many target neuronal populations are physically intermixed with many different neurons. In addition, many target neuronal populations are effectively inaccessible using current delivery methods. Accordingly, there exists a need for a method which can be used to conveniently provide a gene delivery vector to a target neuron where access to target neuron is restricted. The invention described herein provides such a mechanism.